These Tnfsf4 knock-out mice are completely protected from diabetes and histological evaluation seldom shows insulitis.
Christophe Benoist, Joslin Diabetes Center
Tnfsf4tm1Shrhomozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. There is no detectable expression of Tnfsf4 on activated dendritic cells, T-cells and B-cells derived from spleen or lymph nodes by FAC analysis or ELISA. Additionally, the number of B-cells, T-cells, T-cell subsets and expression of CD25 and CD69 in spleen and lymph nodes are comparable to NOD controls. All Tnfsf4 homozygous mice are completely protected from diabetes and histological evaluation seldom shows insulitis when compared to wild-type controls, which exhibit a normal NOD like diabetes incidence and onset.
This model is useful for studying co-stimulation, dendritic cell function and the role of Tnfsf4 on CD4 positive T cell responses in Type 1 Diabetes.
A construct containing a neomycin expression cassette replaced the entire extracellular domain and part of the 3' untranslated region of Tnfsf4 (commonly referred to as Ox40l and cloned from 129/Sv mouse genomic library) was transfected into J1 embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. To establish a colony with germ line transmission, chimeric mice were backcrossed to 129/Sv (Chen et, al, 1999). Martin-Orozco et al. 2003, subsequently backcrossed this mutation to NOD/Lt. A genome wide scan confirmed that markers for Idd1, Idd3, Idd5 and Idd10 were homozygous for the NOD allele. In 2004, the Type 1 Diabetes Resource received NOD.129(B6)-Tnfsf4tm1Shr/DoiJ at generation N8F4.
|Allele Name||targeted mutation 1, Arlene H Sharpe|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Arlene H Sharpe; Tnfsf4tm1Shr|
|Gene Symbol and Name||Tnfsf4, tumor necrosis factor (ligand) superfamily, member 4|
|Gene Synonym(s)||Ath-1; Ath1; atherosclerosis 1; CD252; tax-transcriptionally activated glycoprotein 1 ligand; TXGP1; Txgp1l; Ath-1; Ath1; Ox40l; OX-40L; OX40L; Txgp1l; OX4OL; GP34; Ox40 ligand; CD134L; gp34; Ox40l; Tnlg2b; TNLG2B|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin selection cassette inserted by homologous recombination replaced the exon encoding the entire extracellular domain and a portion of the 3' untranslated region. Protein was undetected by flow cytometric analysis of activated homozygous mutant dendritic cells.|
|Mutations Made By|| |
Arlene Sharpe, Harvard Medical School
|Homozygous for Tnfsf4<tm1Shr>, 1 pair minimum|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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